Amino hindered

Chlorosulfonyl isocyanate is an excellent alternative to alkaline cyanates ia the preparation of hydantoias from stericaHy hindered or labile amino nitriles (62). Imino derivatives similar to (18) can also be obtained by addition of sonitnles to imines followed by treatment with a cyanate (63). 

Yields depend on the reactivity of the amines and the choice of reaction conditions, including the choice of copper catalyst. Generally, the reactivity increases with increasing amine basicity. Thus, i7n7-toluidine (pTf = 5.1) reacts four times faster than aniline (pif = 4.7) (27). StericaHy hindered amines such as 3,5-di-amino-2,4,6-trimethylbenzenesulfonic acid react very slowly. 

A mechanism has been proposed to rationalize the results shown in Figure 23. The relative proportion of the A -pyrazolines obtained by the reduction of pyrazolium salts depends on steric and electronic effects. When all the substituents are alkyl groups, the hydride ion attacks the less hindered carbon atom for example when = Bu only C-5 is attacked. The smaller deuterohydride ion is less sensitive to steric effects and consequently the reaction is less selective (73BSF288). Phenyl substituents, both on the nitrogen atom and on the carbon atoms, direct the hydride attack selectively to one carbon atom and the isolated A -pyrazoline has the C—C double bond conjugated with the phenyl (328 R or R = Ph). Open-chain compounds are always formed during the reduction of pyrazolium salts, becoming predominant in the reduction of amino substituted pyrazoliums. 

A methyl group at C-16 hinders addition to the double bond and the reaction then proceeds normally and in good yield to the 16-methyl-17-acetyl-amino steroid, which gives the 16j9-methyl-17-ketone on hydrolysis. 

The -butyl ester is a relatively hindered ester, and many of the following methods for its formation should be, and in many cases are, equally effective for the preparation of other hindered esters. The related 1- and 2-adamantyl esters have been used for the protection of aspartic acid and other amino acids (1-AdOH, toluene, dimethyl sulfate, cat. TsOH, 70-80% yield). ... 

B0C)20, Mc4N0H-5H20, CH3CN, 88-100% yield. These conditions were found to be very good for sterically hindered amino acids. ... 

PhCH20COCl, Na2C03, H20,0°, 30 min, 72% yield. Alpha-omega diamines can be protected somewhat selectively with this reagent at a pH between 3.5 and 4.5, but the selectivity decreases as the chain length increases [H2N(CH2) NH2, n = 2, 71% mono n = l, 29% mono]. Hindered amino acids are protected in DMSO (DMAP, TEA, heat, 47-82% yield). These conditions also convert a carboxylic acid to the benzyl ester. ... 

Reductive alkylation with chiral substrates may afford new chiral centers. The reaction has been of interest for the preparation of optically active amino acids where the chirality of the amine function is induced in the prochiral carbonyl moiety 34,35). The degree of induced asymmetry is influenced by substrate, solvent, and temperature 26,27,28,29,48,51,65). Asymmetry also has been obtained by reduction of prochiral imines, using a chiral catalyst 44). Prediction of the major configurational isomer arising from a reductive alkylation can be made usually by the assumption that amine formation comes via an imine, not the hydroxyamino addition compound, and that the catalyst approaches the least hindered side (57). 

Dinitroarenes containing substituents such as hydroxyl or amino groups are reduced with 3 mol equiv of hydrazine hydrate in the presence of Raney nickel to afford selectively a compound in which only one nitro group is reduced. In general, the main product is derived by reduction of the more hindered nitro function. For example,... 

This method was effective for acylation of a hindered tertiary alcohol in the anticancer agent camptothecin by protected amino acids. 

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